Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 196K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Grumont, R. J. Articles by Gerondakis, S. Search for Related Content PubMed PubMed Citation Articles by Grumont, R. J. Articles by Gerondakis, S. Social Bookmarking                            What's this?

Articles

B Lymphocytes Differentially Use the Rel and Nuclear Factor B1 (NF-B1) Transcription Factors to Regulate Cell Cycle Progression and Apoptosis in Quiescent and Mitogen-activated Cells

Raelene J. Grumont^*, Ian J. Rourke^*, Lorraine A. O'Reilly^*, Andreas Strasser^*, Kensuke Miyake, William Sha, and Steve Gerondakis^*

From ^* The Walter and Eliza Hall Institute of Medical Research, Post Office The Royal Melbourne Hospital, Victoria 3050, Australia; the Department of Immunology, Saga Medical School, Nabeshima, Saga 849, Japan; and the University of California, Berkeley, California 94720

Rel and nuclear factor (NF)-B1, two members of the Rel/NF-B transcription factor family, are essential for mitogen-induced B cell proliferation. Using mice with inactivated Rel or NF-B1 genes, we show that these transcription factors differentially regulate cell cycle progression and apoptosis in B lymphocytes. Consistent with an increased rate of mature B cell turnover in naive nfkb1^–/– mice, the level of apoptosis in cultures of quiescent nfkb1^–/–, but not c-rel^–/–, B cells is higher. The failure of c-rel^–/– or nfkb1^–/– B cells to proliferate in response to particular mitogens coincides with a cell cycle block early in G1 and elevated cell death. Expression of a bcl-2 transgene prevents apoptosis in resting and activated c-rel^–/– and nfkb1^–/– B cells, but does not overcome the block in cell cycle progression, suggesting that the impaired proliferation is not simply a consequence of apoptosis and that Rel/NF-B proteins regulate cell survival and cell cycle control through independent mechanisms. In contrast to certain B lymphoma cell lines in which mitogen-induced cell death can result from Rel/NF-B–dependent downregulation of c-myc, expression of c-myc is normal in resting and stimulated c-rel^–/– B cells, indicating that target gene(s) regulated by Rel that are important for preventing apoptosis may differ in normal and immortalized B cells. Collectively, these results are the first to demonstrate that in normal B cells, NF-B1 regulates survival of cells in G0, whereas mitogenic activation induced by distinct stimuli requires different Rel/NF-B factors to control cell cycle progression and prevent apoptosis.

This work is supported by the National Health and Medical Research Council (Australia), the Anti-Cancer Council of Victoria, the Australian Cooperative Research Centre grant (No. 91007), and Commonwealth AIDS Research Grant (No. 971274).

Address correspondence to Steve Gerondakis, The Walter and Eliza Hall Institute of Medical Research, P.O. The Royal Melbourne Hospital, Victoria 3050, Australia. Phone: 61-3-93452542; Fax: 61-3-93470852; E-mail: gerondakis{at}wehi.edu.au

¹ Abbreviations used in this paper: BrdU, 5-bromo-2-deoxyuridine; mRNA, messenger RNA; PI, propidium iodide.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Dorff, T. B., Goldkorn, A., Quinn, D. I. (2009). Review: Targeted therapy in renal cancer. Therapeutic Advances in Medical Oncology 1: 183-205 [Abstract]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS